Bile acids, obesity, and the metabolic syndrome

Abstract

Bile acids are increasingly recognized as key regulators of systemic metabolism. While bile acids have long been known to play important and direct roles in nutrient absorption, bile acids also serve as signaling molecules. Bile acid interactions with the nuclear hormone receptor farnesoid X receptor (FXR) and the membrane receptor G-protein-coupled bile acid receptor 5 (TGR5) can regulate incretin hormone and fibroblast growth factor 19 (FGF19) secretion, cholesterol metabolism, and systemic energy expenditure. Bile acid levels and distribution are altered in type 2 diabetes and increased following bariatric procedures, in parallel with reduced body weight and improved insulin sensitivity and glycemic control. Thus, modulation of bile acid levels and signaling, using bile acid binding resins, TGR5 agonists, and FXR agonists, may serve as a potent therapeutic approach for the treatment of obesity, type 2 diabetes, and other components of the metabolic syndrome in humans.

Metabolic Biomarkers for Prognostic Prediction of Pre-diabetes: results from a longitudinal cohort study

“…LysoPCs can mediate many cell-signaling pathways in monocytes/macrophages 29,31 and specific receptors 32 , and therefore participate in the inflammatory response. In our results, several lysoPC species (LPC C20:4, LPC C18:3, LPC C20:5, LPC C20:3) were down-regulated from pre-DM to NGR group, while the plasma level of LPC C18:1 were higher and LPC C18:0 were lower in DM than pre-DM patients, possibly owing to altered activity of phospholipase A2 which catalyzes PC hydrolysis to lysoPC 33 .…”

Neuroendocrine adaptations to bariatric surgery

“…Bile acids are now recognised to have effect beyond the absorption of fats, fat soluble vitamins and cholesterol metabolism by having a broader influence on obesity, type 2 diabetes and features of the metabolic syndrome (Lefebvre et al, 2009;Ma and Patti, 2014). Primary bile acids, synthesised from cholesterol in the liver, are stored in the gallbladder and secreted into the second part of the duodenum in response to a meal.…”

“…Primary bile acids, synthesised from cholesterol in the liver, are stored in the gallbladder and secreted into the second part of the duodenum in response to a meal. Bile acids are actively and passively absorbed in the terminal ileum and effectively recycled via the portal vein to the liver where they may be secreted again into the bile, an enterohepatic cycle that can be completed many times a day (Ma and Patti, 2014). The bile acid pool is self-regulated largely through the nuclear farnesoid X receptor (FXR) and a number of additional feedback pathways.…”

Increased Bile Acid Synthesis and Deconjugation After Biliopancreatic Diversion

“…Several studies have shown that plasma BAs increase after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (8–11). Because BAs can act in an endocrine fashion to regulate a variety of glucose and lipid metabolic pathways (12–15), it has been speculated that increased BAs may contribute to at least some of the metabolic improvements after surgery (16,17). Indeed, it was recently shown that the BA receptor farnesoid X receptor (FXR) is required for metabolic improvements in mice subjected to sleeve gastrectomy (18).…”